Chemoinformatique TP

Transcription

1 Chemoinformatique TP Jean-Loup Faulon jfaulon.wikispaces.com Répondez aux questions dans un fichier ou sur papier (scanné) et envoyez un fichier pdf à une fois terminé. Indiquer dans le fichier votre nom ainsi que les numéros de TP et questions. Merci de ne pas envoyer de fichier zip ou tar (pdf uniquement, je ne corrigerai pas les autres fichiers) Jean- Loup Faulon / chemo- informa4que 1

2 TP1 Exercice des SMILES aux structures 1. Donnez les structures des SMILES suivants OC(=O)C1CCCCC1 NC(Cc1ccc(O)cc1)C(O)=O C1=CC2=C(C=C1)C=CC=C2 C12C3C4C1C5C2C3C45 KNIME tips: With file readers Make sure output is smiles not string You can also use Marvin sketch within KNIME and paste the string 2. Donnez les SMILES des structures et réaction suivantes KNIME tips: With Marvin sketch choose smiles as an output Jean- Loup Faulon / chemo- informa4que 2

3 TP1 Exercice algorithme de Morgan 3. Donnez le nombre d équivalence (i.e. le nombres de classes de symétrie entres atomes) du phenylmethanethiol et du 1,8-dimethylnaphthalene 4. Donnez les SMILES canoniques de ces deux structures KNIME tips: Draw with Marvin sketch choose smiles as an output Symmetries are found in Community node / CDK / Symmetry Canonicalization is in CDK or RDKit Jean- Loup Faulon / chemo- informa4que 3

4 TP2 Predicting alkanes boiling point with KNIME, Download TPdes.tar.gz at jfaulon.wikispaces.com / Teaching pages Read smiles and boiling point in the file BP.txt. Compute Zagreb index and molecular weight (you can try other descriptors as well) for each SMILES. Run the QSAR using LOO and linear 10-fold as cross validation with 1) linear regression and 2) polynomial regression. Comment your results and send all parameterization details, measured vs. prediction plots as well as all regression coefficients (including Q2) to jean-loup.faulon@issb.genopole.fr. Zagreb indices: Summary of the runs to perform Zagreb index, linear regression, LOO Zagreb index, linear regression, linear 10-fold MW, linear regression, LOO MW, linear regression, linear 10-fold Zagreb index, polynomial regression, LOO Zagreb index, polynomial regression, linear 10-fold MW, polynomial regression, LOO MW, polynomial regression, linear 10-fold Jean- Loup Faulon / chemo- informa4que 4

5 TP3 criblage virtuel with KNIME Download TPscreen.tar.gz at jfaulon.wikispaces.com / Teaching pages Write a KNIME workflow that reads all E. coli metabolites and all Drugbank approved drugs and search using similarity tools the closest E. coli metabolite for each drug. For E. coli (EcoCyc database) metabolite the file is provided in TPscreen. For drugs, download the SDF (aproved drug only) from Drugbank. Try different fingerprints (MACCS, PubChem, ECFP6) and give for each the number of drugs having a E. coli metabolite for which Tanimoto = 1. Give- the list of drugs having a Tanimoto = 1 for all fingerprints.. Comment your results and send all parameterization details, and the list you have compiled to jean-loup.faulon@issb.genopole.fr. Jean- Loup Faulon / chemo- informa4que 5

6 TP3 criblage virtuel with KNIME Download TPscreen.tar.gz at jfaulon.wikispaces.com / Teaching pages DB ID name E coli name 1 DB00122 Choline CHOLINE 2 DB00147 Pyridoxal PYRIDOXAL 3 DB00152 Thiamine THIAMINE 4 DB00165 Pyridoxine PYRIDOXINE 5 DB00170 Menadione CPD DB00194 Vidarabine ADENOSINE CPD DB00266 Dicoumarol DICOUMAROL 8 DB00339 Pyrazinamide PYRAZINAMIDE 9 DB00435 Nitric Oxide NITRIC- OXIDE 10 DB00440 Trimethoprim CPD DB00515 CisplaUn CPD DB00544 Fluorouracil CPD DB00581 Lactulose CPD DB00583 L- CarniUne CARNITINE D- CARNITINE 15 DB00584 Enalapril CPD DB00594 Amiloride CPD DB00605 Sulindac CPD DB00640 Adenosine ADENOSINE CPD DB00677 Isoflurophate DIISOPROPYL- FLUOROPHOSPHATE 20 DB00727 Nitroglycerin CPD DB00730 Thiabendazole THIABENDAZOLE 22 DB00742 Mannitol GALACTITOL MANNITOL SORBITOL 23 DB00780 Phenelzine CPD DB00819 Acetazolamide CPD DB00859 Penicillamine CPD DB00864 Tacrolimus CPD DB00898 Ethanol ETOH 28 DB00951 Isoniazid ISONIAZIDE 29 DB00987 Cytarabine CYTIDINE 30 DB01034 Cerulenin CPD DB01093 Dimethyl sulfoxide DMSO 32 DB01110 Miconazole CPD DB01140 Cefadroxil CPD DB01197 Captopril CPD DB01213 Fomepizole CPD DB01265 Telbivudine THYMIDINE 37 DB01326 Cefamandole CPD DB01356 Lithium LI+ 39 DB01440 Gamma Hydroxybutyric Acid 4- HYDROXY- BUTYRATE 40 DB01598 Imipenem CPD DB01626 Pargyline CPD DB03166 AceUc acid ACET 43 DB06690 Nitrous oxide NITROUS- OXIDE 44 DB06770 Benzyl alcohol BENZYL- ALCOHOL 45 DB06782 Dimercaprol 23- DIMERCAPTOPROPAN- 1- OL 46 DB08604 Triclosan CPD Jean- Loup Faulon / chemo- informa4que 6

7 TP extra avec le logiciel Marvin dans KNIME 1. Lancez MarvinSketch 2. Dessinez le chlorobenzne et familiarisez-vous avec les icones et les menus, files, edit, view (transform, display, misc), structure et tools 3. Donnez les SMILES des produits suivants: acide acétique, 2-aminoacetic acid, 2-amino-3- methylpentanoic acid, 1-chloro-3-methylbenzene, (3Z)-hex-3-ene, (2S,3S)-2-amino-3- methylpentanoic acid, (2R,3R)-2-amino-3-methylpentanoic acid, (2E)-1-choro-pent-2-ene, (1R, 3S) cyclohexane-1,3-diol, 2,7-dimethylnaphthalene 4. La plus petite fullerene C 20 H 20 est représentée dans la figure à droite, donnez pour cette molécule - Sa masse - Son énergie (Dreiding) - Le nombres de classes d'équivalences d'atomes de carbones; même question si vous replacez un atome de carbone par de l'azote 5. Créez un fichier test.seq contenant la sequence suivante CAKDLIAC. - Quel est la masse et le point isoélectrique de cette séquence - Modifiez la structure de façon à contenir un pont disulfure, donnez l'énergie de la structure optimisée KNIME note: 1-4. With Marvin sketch choose smiles as an output Energy can be calculated using Community node / RDKit optimise geometry, mass in in RDKit / Calculator / Descriptot 5. Create a fasta file load it with Marvin Sketch Pi can be computed directly with Marvin, save the structure in mol format (can be used later to add the disulfur Jean- Loup Faulon / chemo- informa4que bridge) see 1-4 for the rest 7